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Scientific advances over the past decade have contributed to a much greater understanding of the growth of the human brain from birth to adulthood. Latest evidence illuminates the adolescent brain as a ‘work in progress’, and adolescence as a critical period to build on early investments, offering a second chance for those who have not fared well in early childhood. Neuroscientific research in particular is integral to improving our understanding of the cerebral transformations that take place during this time and how they are influenced by interactions between the evolving adolescent brain and the environment in which it develops. In the field of early childhood development (ECD), neuroscientific evidence featured prominently in galvanizing positive change for children through changes in policy and programming and more of this type of evidence is needed to also provide answers regarding critical intervention junctures and approaches during adolescence. In this compendium, eight experts in adolescent neuroscience and development summarize scientific and programmatic evidence from their work, offering an insight into how to maximize the potential of adolescents during this period of opportunity, but also vulnerability. It builds on the discussions initiated at a one-day symposium entitled The Adolescent Brain: A second window of opportunity, held on 4 May 2016 at UNICEF headquarters in New York. The event brought together specialists to review the state of science related to the adolescent brain, specifically focusing on how to guide future responses to programming and policy and providing directions for research to further advance these aims. The advances and investments made in ECD must be continued for children in their second decade of life. Adolescence is a time of both opportunity and vulnerability. Many problematic and risky behaviours are activated in adolescence, including substance abuse, and behaviours that can lead to sexually transmitted diseases HIV/AIDS, road injuries, drowning and other negative outcomes (Mokdad, 2016). It is a time when mental illness and the incidence of suicide sharply increases (Petroni, Patel and Patton, 2016) and when experiences of bullying, inter-personal violence and exclusion often leave a long-term mark on the individual (Lupien, 2012). The commentaries in this compendium together summarize the state of adolescent neuroscience, reflecting on what is known about positive and negative impacts on brain development, including the effects of poverty, violence, stress, technology, but also socio-emotional learning, meditation, nutrition, counselling and positive relationships. They go beyond the science to discuss its application for maximizing the potential of adolescents. This compendium is designed to encourage further dialogue stimulated by new thinking grounded in adolescent neuroscience research and its application. It aims to challenge readers to bring science to bear on programme interventions and public policies for adolescents. An improved understanding from neuroscience is well-placed to strengthen behavioural evidence and provide a more complete picture of adolescent behaviour and development, while also stimulating fresh thinking and approaches that can be tested.